The Role Of Tob In The Rat Learning And Memory

Tob is a negative cell cycle regulator with anti-proliferative activity in theperiphery. It is a member of PC3/TIS21/BTG/TOB family. Using a behavioralscreening paradigm to look for novel gene functions in the brain, we identified Tobas a brain-expressed protein involved in learning and memory. Behavioral trainingof fear-conditioning triggered a transient elevation of Tob protein, which occurredat the critical period of memory consolidation. Functional perturbation of Tob byintra-CA1 infusion of antisense oligonucleotide in rats impaired spatial learningand memory in Morris water maze and long-term memory for contextual fearconditioning, two behavioral paradigms that require the hippocampus. Furthermore,long-term potentiation (LTP) was suppressed by infusion of Tob antisenseoligonucleotide into the CA1 region. Together, these results indicate that thenegative cell cycle regulator, Tob, is involved in hippocampus-dependent learningand memory.Tob has higher expression in both the hippocampus and the cerebellum. Ourprevious study indicates that Tob in the hippocampal CA1 region is involved indeclarative learning and memories that require the hippocampus. The present studyinvestigates if Tob is important for non-declarative learning and memory, namely,motor learning and coordination that require the cerebellum. Our results shows that,Tob expression was increased in cerebellum after rats were trained in the rotorod task;Rats with infusion of Tob antisense oligonucleotide into the 4th ventricle had a poorerperformance in a beam crossing task: the number of slipping was significantly moreand the time spent on beam-crossing significantly longer in relative to the controlanimals;Rats with infusion of Tob antisense oligonucleotide into the 4th ventricleshowed a deficit in motor coordination when placed on a rotating rod: the time for theanimals to stay on the rotating rod was significantly shorter in relative to that for thecontrol animals to do. The present results indicate that Tob is engaged in motorlearning and coordination.